This is continuing study of hypertensive subjects, their nuclear families and extended pedigrees. The long term goal is to understand the pathophysiology of different types of essential hypertension (HBP). Defining the specific causes and cardiovascular disease risks of different types of HBP will lead to better methods for detection, assessment, treatment and prevention of HBP. (e.g. some may need drug Rx more than others, etc.) An informative battery of special cation tests, special blood pressures, other pertinent variables, and a detailed medical family history (FHx) have been collected on 2548 subjects in 98 extended pedigrees in Utah. Special cation tests appear to be largely genetically determined and involved in the pathophysiology of HBP. Cation tests under study include: Na-Li Countertransport; Li-K Cotransport; intracellular Na,K,Mg; Na-K ATPase pump activity and binding sites; and plasma levels of Na, K, Mg, ionized Ca and digoxin-like pump inhibitor. Special BP's include sitting, standing, lying, tilting, and BP during venipuncture, mental arithmetic, bicycle exercise, isometric handgrip exercise, and 24 hour ambulatory monitoring. Other variables informative in preliminary analyses include detailed anthropometics, blood lipids, stress and exercise questionnaires, urine electrolytes, plasma renin activity, urinary kallikrein, and detailed FHx of HBP, CHD and CYA. Five proposed specivic aims include: 1. Continue statistical and pedigree analyses of data already collected on 2548 subjects. 2. Perform the same tests on 600 new, population-based HBP subjects on drug Rx and again 4 months after interruption of drug Rx to obtain unconfounded values of biochemical and BP tests. 3. Test for specific subtypes of HBP among these 600 subjects using individual variables and multivariate combinations of variables. Characterize specific HBP syndromes. 4. Screen 300 nuclear families (N=1200) to test for familiality of subtype indicators and to identify those HBP subtype indicator variables deserving detailed pedigree analysis. 5. Study 1000 sequentially sampled persons in 40 extended pedigrees to test for major genes, DNA probe linkage, and gene-environment interactions as determinants of specific types of hypertension.